Osteoarthritis (OA) is the leading cause of functional disability in the United States, impacting half of adults over the age of 65. Pain and physical function, however, are often poorly associated with radiographic measures of joint pathology. Research clarifying the factors associated with symptom expression that contribute to the development of novel prevention and management strategies is needed. Chronic insomnia is one likely factor, which occurs in ~50% of knee OA patients, but the consequences, mechanisms and management of insomnia in OA is poorly understood. Our experimental work indicates that sleep disturbance may be both a risk factor for and a consequence of chronic pain, and that sleep disruption directly alters central pain processing. These pain processing changes amplify pain perception, and we hypothesize they may contribute to pain persistence and its detrimental physical and emotional consequences in OA. This ancillary proposal enhances our ongoing Sleep in Osteoarthritis Project [SOAP (R01AR054871)], a large-scale investigation of four well-characterized groups of older adults: matched healthy controls and knee OA patients with and without insomnia. The parent project includes a clinical trial to determine whether sleep disturbance impairs central pain processing and modulation in OA, using state-of-the-science quantitative sensory testing methods, and determines whether cognitive behavioral therapy for insomnia (CBT-I) improves short and long-term sleep and clinical pain in OA. Based on emerging sleep and pain research, we hypothesize in this ancillary proposal that aberrant inflammatory activity may represent a common neurobiologic mechanism by which sleep disruption contributes to pain augmentation, physical limitations and mood disturbance. To test this hypothesis, we will integrate into the parent study: a) assessments of resting and pain-evoked inflammation;b) a brief battery of standardized physical performance tests;c) unobtrusive daily measurements of physical function (actigraphy);and d) formal assessments of pain-evoked and daily mood disturbance. The Specific Aims of this ancillary proposal are to: 1) characterize the complex inter- relationships between resting and pain-evoked inflammation and pain, physical function and mood disturbance in older adults;2) determine whether OA and/or insomnia are associated with elevations in resting and pain-evoked inflammation;and 3) determine whether CBT-I decreases resting and pain-evoked inflammation, and whether changes in inflammation mediate improvements in pain, physical function and mood in OA patients with insomnia. Both insomnia and inflammation are modifiable via behavioral and pharmacologic therapies. Therefore, the proposed project is likely to generate findings that will have a novel and substantial impact on the prevention, management and treatment of OA.